ZEB1 induces non-small cell lung cancer development by targeting microRNA-320a to increase the expression of RAD51AP1.

Abstract

Lung cancer is the most prevalent cancer worldwide, with its mortality rate reported to be in millions annually; one of the two subtypes is non-small cell lung cancer (NSCLC). In this study, we investigated the interactions and expressions of zinc finger E-box binding homeobox 1 (ZEB1), microRNA-320a (miR-320a) and RAD51-associated protein 1 (RAD51AP1) in NSCLC tissues to determine the roles of ZEB1 in regulation of miR-320a and RAD51AP1 in the development and metastasis of NSCLC. First, the expression levels of miR-320a and ZEB1 were quantified in NSCLC tissues and cells. Transfection assay was conducted to identify the effects of miR-320a on the progression of NSCLC cells. The interaction of miR-320a with ZEB1 and RAD51AP1 was predicted and verified using dual-luciferase reporter gene assay and chromatin immunoprecipitation assay. Finally, subcutaneous xenograft tumors of 6-week mice and metastatic model tumors of 8-week mice were established to further explore the in vivo effect of miR-320a/ZEB1/RAD51AP1 on NSCLC. The findings revealed a lower expression of miR-320a in NSCLC tissues and cells, while this result was reversed regarding ZEB1 expression. ZEB1 suppressed miR-320a expression and upregulation of miR-320a resulted in the reduction of proliferation, invasion and metastasis rate of NSCLC cells, and promoted NSCLC cell apoptosis. ZEB1 promoted the expression of RAD51AP1 via inhibition of miR-320a, promoting tumor growth in vivo. ZEB1 transcriptionally inhibited the expression of miR-320a and upregulated the expression of RAD51AP1, thereby promoting metastasis in NSCLC.

• Authors: Huifeng Wang, Hui Dong, Lijiao Qiao, Yuanyuan Wu, Bo Wu, Xiangming Jin
• Journal: Experimental cell research (Exp Cell Res) Vol. 405 Issue 2 Pg. 112687 (08 15 2021) ISSN: 1090-2422 [Electronic] United States
• PMID: 34097859 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021. Published by Elsevier Inc.

Chemical References

• DNA-Binding Proteins
• MIRN320 microRNA, human
• MicroRNAs
• RAD51AP1 protein, human
• RNA-Binding Proteins
• ZEB1 protein, human
• Zinc Finger E-box-Binding Homeobox 1

Topics

• Animals
• Carcinoma, Non-Small-Cell Lung (genetics, metabolism)
• Cell Line, Tumor
• Cell Movement (genetics)
• Cell Proliferation (genetics)
• DNA-Binding Proteins (metabolism)
• Gene Expression Regulation, Neoplastic (genetics)
• Humans
• Lung Neoplasms (genetics, metabolism, pathology)
• Mice, SCID
• MicroRNAs (genetics)
• Neoplasm Invasiveness (genetics)
• RNA-Binding Proteins (metabolism)
• Zinc Finger E-box-Binding Homeobox 1 (genetics, metabolism)
• Mice